Catalytic hydrogenation of N-4-nitrophenyl nicotinamide in a micro-packed bed reactor
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Abstract
Recent advancements in micro-flow technologies and a drive toward more efficient, greener and safer processes have led to a renaissance in flow-chemistry for pharmaceutical production. In this work, we demonstrate the use of a stabilized Pd nanoparticle-organic-silica catalyst to selectively catalyze the hydrogenation of N-4-nitrophenyl nicotinamide, a functionalized active pharmaceutical ingredient (API) surrogate. Extensive catalyst and reactor characterization is provided to establish an in-depth understanding of the unique multiphase dynamics within the micro-packed bed reactor, including the identification of a large liquid holdup (74-84%), rapid multiphase mass transfer (k(m)a > 1 s(-1)), and liquid residence time distributions. A kinetic analysis has revealed that the surface catalyzed hydrogenation progresses through a condensation mechanism whereby an azo dimer intermediate is formed and rapidly consumed. Finally, a parametric study was performed at various pressures, temperatures, residence times and flow regimes to achieve quantitative chemoselective conversion of the nitroarene to the corresponding primary amine.
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Affiliations
- Massachusetts Institute of Technology (MIT) (MIT)
- University of Cambridge
- Novartis Pharma AG
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Classification Areas
- API